1. Technical Field
The invention relates to a process for preparing an optionally substituted 4-(benzimidazol-2-ylmethylamino)-benzamidine, wherein    (a) an optionally correspondingly substituted diaminobenzene is condensed with 2-[4-(1,2,4-oxadiazol-5-on-3-yl)-phenylamino]-acetic acid and    (b) i) the product thus obtained is hydrogenated and            ii) optionally the amidino group is carbonylated without isolating the intermediate product of the hydrogenation beforehand.        
The 4-(benzimidazol-2-ylmethylamino)-benzamidine thus obtained may subsequently be converted into a salt.
Moreover, the invention relates to a process for preparing a salt of an optionally substituted 4-(benzimidazol-2-ylmethylamino)-benzamidine, wherein    (a) an optionally correspondingly substituted diaminobenzene is condensed with 2-[4-(1,2,4-oxadiazol-5-on-3-yl)-phenylamino]-acetic acid,    (b) the product thus obtained is hydrogenated, and    (c) i) optionally the amidino group is carbonylated and            ii) without prior isolation of the intermediate product of the carbonylation the desired salt is isolated.        
2. Prior Art
Substituted (4-benzimidazol-2-ylmethylamino)-benzamidines, particularly 1-methyl-2-[N-[4-(N-n-hexyloxycarbonylamidino)phenyl]-amino-methyl]-benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)-amide are already known from International Patent Application WO 98/37075 as active substances with a thrombin-inhibiting and thrombin time prolonging activity.
The main types of indication for the compound of chemical formula I are the postoperative prevention of deep vein thrombosis and the prevention of stroke (prevention of stroke due to atrial fibrillation, SPAF for short).
In WO 98/37075 it is proposed that the substituted (4-benzimidazol-2-ylmethylamino)-benzamidines be prepared by reacting the corresponding substituted (4-benzimidazol-2-ylmethylamino)-benzonitriles with ammonia. This process is highly complex from the point of view of production technology and results in a high loading of acids that have to be disposed of.
The aim of the present invention was to indicate an alternative method of preparing the substituted (4-benzimidazol-2-ylmethylamino)-benzamidines, by which this technologically complex step could be avoided.